Signal transduction is the general process by which cells respond to extracellular signals. Extracellular signals are mediated through a cascade of biochemical reactions that begins with the binding of a signal molecule, e.g., a hormone, neurotransmitter, or growth factor, to a cell membrane receptor, and ends with the activation of an intracellular target molecule. This process of signal transduction regulates all types of cell functions including cell proliferation, differentiation, and gene transcription.
G-protein signaling is one of the important pathways of signal transduction. Specifically, receptors on a cell surface are coupled to a G-protein on the plasma membrane of the cell. The G-protein becomes activated when the receptor binds a messenger molecule, GTP. Activation of the G-protein leads to the production of the second messenger molecule, cAMP, which controls phosphorylation and activation of other intracellular proteins. The G-protein is deactivated by hydrolysis of the GTP by GTPase.
A second regulatory mechanism of G-protein signaling pathway involves a family of mammalian gene products termed regulators of G-protein signaling (RGS; Druey, K. M. et al. (1996) Nature 379: 742-746). These proteins negatively regulate the G-protein pathway by an unknown mechanism. Some 15 members of the RGS family have been identified. RGS family members are related structurally through similarities in an approximately 120 amino acid region termed the RGS domain and functionally by their ability to inhibit the interleukin (cytokine) induction of MAP kinase in cultured mammalian 293T cells (Druey et al., supra).
The first RGS family member BL34(RGS1) was found in activated B-lymphocytes associated with chronic lymphocytic leukemia (Hong, J. X. et al. (1993) J. Immunol. 150:3895-3904). RGS1 inhibits the activation of MAP kinase, a G-protein mediated event, which is induced by the binding of platelet-activating factor to a B-cell receptor. RGS2 (GOS8) was likewise found in lectin-stimulated peripheral blood mononuclear cells. Sequence similarities were noted between RSG2 and various genes involved in immune regulation of retroviruses and suppression of oncogenes (Siderovski D. P. et al. (1994) DNA Cell Biol. 13(2): 125-147).
RGS proteins regulate the G-protein signaling pathways directly by their ability to bind and inhibit G-protein function. Therefore, the discovery of new RGS proteins and the polynucleotides which encode them satisfies a need in the art by providing new diagnostic or therapeutic compositions useful in diagnosing, preventing, and treating disorders associated with cell proliferation and inflammation.